Chemical exchange processes in tissue may be visualized using magnetic resonance imaging (MRI) employing a chemical exchange saturation transfer (CEST) methodology. CEST imaging exploits the ability of nuclear magnetic resonance (NMR) to resolve different signals arising from protons of different molecules. CEST techniques operate by detecting the exchange mediated saturation transfer between bound and bulk protons by utilizing exchanging groups (e.g., —OH and —NH) of small organic molecules. In particular, the transfer of magnetization from the exchange group and/or contrast agent attenuates the bulk water signal. This attenuation of the bulk water signal can be measured and used to provide contrast in MRI.
FIG. 1A illustrates the principle behind CEST techniques. In particular, FIG. 1A illustrates exchange kinetics ka and kb between the bulk protons (A) and the bound protons (B). When RF irradiation is applied at a frequency of the chemical shift of an exchanging group (e.g., —OH or —NH) as shown in FIG. 1B (RF ON), the RF saturation is transferred to the surrounding bulk water molecules resulting in a relatively small yet detectable decrease in the strong water signal (i.e., negative contrast is generated). CEST imaging is relatively sensitive to the environment of the exchanging group and/or contrast agent and has found a number of applications such as the detection of pH, metabolite levels, protein depletion, etc.
CEST techniques may be supplemented or complemented by using paramagnetic complexes as MRI contrast agents. Such techniques are referred to as PARACEST. For example, exogenous paramagnetic lanthanide complexes exhibit slow exchange kinetics between an inner coordination site and bulk water and show large chemical shifts for lanthanide-bound water molecules. Similar to the CEST effect, PARACEST contrast is generated via application of a saturating RF sequence at a frequency corresponding to the chemical shift of the water protons bound to the paramagnetic complex. Utilization of PARACEST may provide several advantages over CEST, for example, PARACEST techniques may provide increased sensitivity enabling detection of the paramagnetic contrast agents in the microMolar concentration range.